The Baltimore Longitudinal Study of Aging (BLSA) was established in 1958 and is one the oldest prospective studies of aging in the USA and the world. The mission of the BLSA is to learn what happens to people as they get old and how to sort out changes due to aging from those due to disease or other causes. Over the last year, we have published a number of papers investigating the effects of possible modifiers of cognitive aging, risk for dementia, and the presence of Alzheimer's pathology at autopsy. In one paper, we applied a new approach using a Disease Progression Scale to investigate domain-specific cognitive trajectories in relation to cognitive impairment. We found that declines in verbal immediate recall were the earliest changes detected but as the underlying disease progressed, verbal delayed recall declines were steeper than those for immediate recall. This finding helps reconcile the observation from prospective studies that changes in immediate recall are evident earliest whereas in clinical settings where impairment is more likely, delayed recall may be more informative. Using data from the BLSA autopsy study, we investigated quantitative measures of amyloid and tau burden in individuals with asymptomatic Alzheimer's disease (ASYMAD) who were clinically normal at death but had sufficient pathology to meet pathological criteria for AD. We previously reported hypertrophy of neuronal cell bodies, nuclei, and nucleoli in the CA1 of the hippocampus (CA1), anterior cingulate gyrus, posterior cingulate gyrus, and primary visual cortex of ASYMAD versus age-matched Control and mild cognitive impairment (MCI) subjects. However, it was unclear whether the neuronal hypertrophy could be attributed to differences in the severity of AD pathology. Here, we performed quantitative analyses of the severity of Beta-amyloid (ABeta) and phosphorylated tau (tau) loads in the brains of ASYMAD, Control, MCI, and AD subjects (n = 15 per group) from the Baltimore Longitudinal Study of Aging. Tissue sections from CA1, anterior cingulate gyrus, posterior cingulate gyrus, and primary visual cortex were immunostained for ABeta and tau; the respective loads were assessed using unbiased stereology by measuring the fractional areas of immunoreactivity for each protein in each region. The ASYMAD and MCI groups did not differ in ABeta and tau loads. These data confirm that ASYMAD and MCI subjects have comparable loads of insoluble ABeta and tau in regions vulnerable to AD pathology despite divergent cognitive outcomes. These findings imply that cognitive impairment in AD may be caused or modulated by factors other than insoluble forms of ABeta and tau. In a collaborative NIA project, tissue from BLSA autopies was used to investigate the neuronal RNA-binding protein HuD in AD. We reported the identification of several HuD target transcripts linked to Alzheimer's disease (AD) pathogenesis. HuD interacted with the 3' UTRs of APP mRNA (encoding amyloid precursor protein) and BACE1 mRNA (encoding ABeta-site APP-cleaving enzyme 1) and increased the half-lives of these mRNAs. HuD also associated with and stabilized the long noncoding (lnc)RNA BACE1AS, which partly complements BACE1 mRNA and enhances BACE1 expression. Importantly, cortex (superior temporal gyrus) from patients with AD displayed significantly higher levels of HuD and, accordingly, elevated APP, BACE1, BACE1AS, and ABeta than did cortical tissue from healthy age-matched individuals. These findings suggest the possibility that HuD jointly promotes the production of APP and the cleavage of its amyloidogenic fragment, ABeta.